Quantifying nanoparticle adhesion mediated by specific molecular interactions

Receptor-mediated targeting of nanometric contrast agents or drug carriers holds great potential for treating cardiovascular and vascular-associated diseases. However, predicting the ability of these vectors to adhere to diseased cells under dynamic conditions is complex due to the interplay of transport, hydrodynamic force, and multivalent bond formation dynamics. Therefore, we sought to determine the effects of adhesion molecule density and flow rate on adhesion of 210 nm particles, with the goal of identifying criteria to optimize binding efficiency and selectivity. Our system employed a physiologically relevant ligand, the vascular adhesion molecule ICAM-1, and an ICAM-1 specific antibody tethered to the nanoparticle using avidin-biotin chemistry. We measured binding and dissociation of these particles in a flow chamber as a function of antibody density, ligand density, and flow rate, and using a transport-reaction model we distilled overall kinetic rate constants for adhesion and detachment from the binding data. We demonstrate that both attachment and detachment of 210 nm particles can be correlated with receptor and ligand valency and are minimally affected by shear rate. Furthermore, we uncovered a time-dependent mechanism governing particle detachment, in which the rate of detachment decreases with contact time according to a power law. Finally, we use our results to illustrate how to engineer adhesion selectivity for specific molecular targeting applications. These results establish basic principles dictating nanoparticle adhesion and dissociation and can be used as a framework for the rational design of targeted nanoparticle therapeutics that possess optimum adhesive characteristics.